CHICAGO — For outpatient COVID-19, prophylactic anticoagulation with rivaroxaban (Xarelto) did not improve outcomes in patients at high thrombotic risk, the PREVENT trial showed.
Compared with placebo, administering the direct-acting oral anticoagulant (DOAC) for 35 days in non-hospitalized patients with symptomatic COVID-19 who had at least one risk factor for thrombosis did not reduce thromboembolic events or hospitalization or death from all causes in the primary intention-to-treat analysis.
The rate was 3.4% with rivaroxaban versus 3.0% with placebo, based on 22 and 19 events, respectively, among the more than 1,200 trial participants (HR 1.16, 95% CI 0.63-2.15), Gregory Piazza, MD, of Brigham and Women’s. Hospital and Harvard Medical School in Boston, reported at the American Heart Association meeting in Chicago.
“With the caveat that the trial was underpowered to provide a definitive conclusion, these data do not support routine antithrombotic prophylaxis in non-hospitalized patients with symptomatic COVID-19,” he told attendees, noting that the rehearsal stopped soon around one o’clock. third of the planned enrollment due to the decrease in numbers and the severity of the pandemic.
That’s a message consistent with other trials of anticoagulants in ambulatory care for COVID-19, noted Renato Lopes MD, PhD, of the Duke Clinical Research Institute in Durham, North Carolina, who serve as a study speaker at the most recent clinical trials session.
Meta-analysis with the almost universally negative trials that have emerged to date suggested no benefit (OR 0.93, 95% CI 0.70–1.23) for the primary variable, although varied between trials, or for mortality (OR 0.64, 95% CI – 0.25). 1.61).
“The results of this trial, in light of the body of evidence in this field, do not support the routine use of any antithrombotic therapy for outpatients with COVID-19,” Lopes said.
PREVENT randomized 1,284 symptomatic patients with a positive laboratory antigen or PCR test for SARS-CoV-2 recruited through US integrated health networks to rivaroxaban (10 mg) or placebo once daily, stratified by number of days from positive test to randomization. Participants were followed for results without any laboratory or office visits, using electronic case report forms and electronic medical records collected only through telehealth or home visits.
Patients were not enrolled if the initial care plan included hospitalization. Enrollment criteria have also been selected for a higher thrombotic risk group because they require at least one of the following risk factors:
- Age ≥ 60 years
- History of venous thromboembolism (VTE), thrombophilia, coronary or peripheral artery disease, cardiovascular disease or ischemic stroke, cancer, diabetes requiring medication, or heart failure
- BMI ≥35 kg/m2
- Elevated D dimer
The most common risk factors were older age, obesity and diabetes. About a quarter of the participants had at least two risk factors. The average age was 56 years; almost 30% of participants were non-white and about 60% were female.
The primary efficacy endpoint was the first occurrence of a composite of symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, systemic non-central nervous system embolization, all-cause hospitalization, and all-cause mortality the causes until the 35th day.
For this endpoint, the modified intention-to-treat analysis produced a change in directionality compared with the intention-to-treat analysis, although not statistically significant, at a rate of 2.0% with rivaroxaban compared to 2.7% with placebo (HR 0.75, 95). % CI 0.35-1.58). Piazza chalked it up to more hospitalizations before receiving the study drug in the rivaroxaban group, while Lopes suggested the difference merits further investigation.
The first major secondary outcome of the composite of symptomatic VTE, arterial thrombotic events and all-cause mortality also showed no significant difference. An exploratory post hoc analysis suggested fewer combined symptomatic VTE and arterial thrombotic events, particularly ischemic stroke, but Lopes urged caution with these unspecified analyses.
In terms of safety, there were no fatal or critical bleeds in the trial and a “significant but modest” increase in non-major clinically relevant bleeds with rivaroxaban versus placebo.
“We saw an explosion of observational data early in the pandemic suggesting that patients with COVID-19 might benefit from a more intense form of anticoagulation; however, we have also learned to be cautious with observational data when we talk about treatment effects,” Lopes noted. .
That the findings were the opposite of what might have been initially guessed in the pandemic, he said, “illustrated once again why we need randomized trials, as they are the only reliable way to guide medical decisions in clinical practice “.
disclosures
The trial was sponsored by Janssen.
Piazza disclosed research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific, as well as consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific, Janssen, NAMSA, Prairie Education and Research Cooperative. Boston Clinical Research Institute and Amgen.
Lopes disclosed relationships with Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, Sanofi-Aventis, Bayer, Novo Nordisk, and Boehringer Ingelheim.